Project(Summary/Abstract The candidate holds a Ph.D. in Biomedical Engineering from Northwestern University and is currently a Research Associate at Mayo Clinic. His research interests are in the field of cardiovascular tissue engineering. His graduate thesis work involved a molecular biology approach for improving endothelial cell retention to vascular grafts. This led to his postdoctoral work which involves an engineering approach for improving capture and retention of endothelial cells to vascular stents and grafts. His postdoctoral work also involves a tissue engineered cardiac valve project to explore both biological and biosynthetic approaches. The candidate's immediate career goal is to transition from mentored to independent research by completing his postdoctoral training and beginning a tenure track faculty position at a major research university. This will require focusing his current projects into a novel research direction while also receiving additional training that will be needed to successfully complete the current and future projects as an independent investigator. The K99/R00 mechanism is the ideal means of achieving this goal. The candidate's long term career goal is to establish an independent and extramurally funded research program within the field of cardiovascular tissue engineering in order to meaningfully improve patient care and train the next generation of scientists, physicians, and engineers. Research career development during the award will include working with an interdisciplinary mentoring team of clinicians, scientists, and engineers. The candidate's primary mentor, Dr. Amir Lerman, M.D., is the Chair of Cardiovascular Research at Mayo Clinic and provides expertise in endothelial cell and vascular biology. The candidate's co-mentors are Dr. Gurpreet Sandhu, M.D., Ph.D. who is the Chair of the Cardiac Catheterization Laboratory at Mayo Clinic and provides expertise in clinical device prototype design and testing, Dr. Dan Dragomir-Daescu, Ph.D. who is a principal engineer at Mayo Clinic and provides expertise in engineering design and analysis, and Dr. Robert Tranquillo, Ph.D. who is Chair of the Department of Biomedical Engineering at the University of Minnesota and provides expertise in biomedical engineering and cardiovascular tissue engineering. Working with his mentors, the candidate will train in clinical device prototype design, porcine model analysis of novel vascular grafts, ovine model analysis of novel cardiac valves, advanced magnetic nanoparticle synthesis, and advanced electrospinning techniques. The candidate will also train in other essential skills including responsible conduct of research, grantsmanship, communication of research findings, mentoring, and project management. Finally, educational opportunities such a graduate coursework in regenerative medicine, cardiovascular physiology, data analysis, and statistics as well as various research and clinical seminar series will round out the training experience. Mayo Clinic offers a variety of educational and support services through the Graduate School, College of Medicine, Office of Research Education, and Center for Clinical and Translation Science that will facilitate the necessary training. Mayo Clinic is committed to supporting translational research and recently established the Center for Regenerative Medicine as a strategic initiative. World experts in a variety of fields are available for collaboration with th common goal of improving patient care. Mayo also offers a variety of research resources and facilities including core facilities such as the Microscopy and Cell Analysis Core, the Biostatistis Core, the Histology Core, and the Materials and Structural Testing Core. The Division of Engineering features a full machine shop, electrical shop, and glass blowing shop to support research requests for engineering design and development. Mayo also has several animal facilities including the Cardiovascular Innovation Laboratory which features a full cardiac catheterization laboratory dedicated for animal studies. The proposed research project is a natural extension of the candidate's ongoing work that focuses his research in a novel direction to begin the transition to independence. The proposed work addresses the important clinical need of improving the blood compatibility of implanted cardiovascular devices by advancing the magnetic endothelialization approach. The proposed work will develop the next generation of magnetic grafts by using the electrospinning fabrication method to generate magnetic nanofiber biomaterials. The grafts will be tested for mechanical, magnetic, and thrombogenicity properties in vitro. The grafts will then be tested for clinicallyOrelevant outcomes including patency, thrombus formation, and neointimal hyperplasia in a porcine implantation model. These grafts are expected to be an important step in the development towards clinical translation. The proposed work will also develop a novel magnetically-functionalized and aligned nanofiber biomaterial that is optimized for mechanical and magnetic properties. This biomaterial is expected to have a wide range of important applications for targeted delivery of cells, drugs, and proteins. The proposed work will then use a novel biomaterial to fabricate novel cardiac valves capable of magnetic endothelialization. The valves will be tested for mechanical, magnetic, and thrombogenic properties in vitro. The valves will then be tested for clinically-relevant outcomes including function, thrombus formation, and calcification in an ovine implantation model. These valves are expected to demonstrate proof of concept for magnetic endothelialization of valves.